Epidemiological data suggest a link between migraine and the female sex hormones. Indeed, it is known that estrogen affects various brain functions, including pain perception. The prevalence of migraine is similar in boys and girls before puberty, but is 3-fold higher in postpubertal females compared with males. Migraine attacks in women are more likely to occur in the perimenstrual period and occur exclusively so in some women. The acute treatment of menstrual migraine is similar to that of non-menstrually related attacks, but the response to treatment may be less favourable. Perimenstrual prophylaxis, with NSAIDs, triptans or estradiol, is effective in decreasing attack frequency and severity.

The use of oral contraceptives (OCs) may change migraine frequency and severity. Since both migraine and hormonal contraceptive use are risk factors for ischaemic stroke, the use of OCs in women who experience migraine should be made only after consideration of the benefit-risk ratio.

Migraine typically, but not invariably, improves during the last two trimesters of pregnancy, and may worsen in the postpartum period. When using drugs to treat migraine during pregnancy, potential risks to the mother and fetus should be considered.

The prevalence of migraine decreases with advancing age and it improves in many, but not all, women after the menopause. However, in the perimenopausal period, migraine may worsen as a result of fluctuations in estrogen levels. Reducing the estrogen dose and changing the estrogen type or the route of administration of hormone replacement therapy (HRT) from oral to transdermal may reduce headache. Migraine is not a risk factor for stroke in postmenopausal women. When considering symptomatic HRT for postmenopausal migraneurs, the usual indications and contraindications should be applied. HRT may also exacerbate migraine.

The understanding of migraine pathophysiology has evolved from the belief that migraine is a vascular disorder, to evidence that better defines migraine as a neurogenic disorder associated with secondary changes in brain perfusion. There is evidence to suggest that the early phase of migraine pain results from neurogenic infiammation affecting cranial blood vessels and dura. Allodynia, hyperalgesia, and expansion of nociceptive fields occur during most well-established migraine attacks. These clinical features of migraine are evocative of those traditionally associated with neuropathic pain. A hypothesis that defines migraine pain as a unique neuropathic pain disorder can imply the potential for neural plasticity and may provide insight into the mechanisms that underlie the transformation of episodic to chronic forms of migraine. The neuropathic pain model of migraine pathophysiology not only paves the way for mechanism-based treatment strategies that can improve the acute and preventive management of migraine attacks, but also opens the door for the discovery of novel therapeutic targets. It also lends momentum to an understanding of clinically intriguing topics such as opiate-induced hyperalgesia and medication-overuse headache (rebound headache), opioid resistance in the treatment of chronic headache, and disease modification in defending against the potential for migraine transformation.

A comprehensive review of the neurotologic manifestations of migraine is presented, focusing on the most recent publications regarding the epidemiology, clinical presentation, pathophysiology, diagnosis, and management of migraine-related vertigo (MV). A strong association exists between vertigo and migraine, with MV being the most common cause of spontaneous (nonpositional) episodic vertigo. Symptoms can be quite variable among patients and within individual patients over time, creating a diagnostic challenge. MV generally presents with attacks of spontaneous or positional vertigo lasting seconds to days with associated migrainous symptoms. Operational diagnostic criteria have been proposed but are not included in the most recent International Headache Society classification of migraine. Better elucidation of the neurologic linkages between the central vestibular pathways and migraine-related pathways and the discovery of ion channel defects underlying some causes of familial migraine, ataxia, and vertigo have furthered the understanding of MV pathophysiology. Treatment of MV currently parallels that of migraine headache, as proper studies of optimal MV management are just beginning.

The association between migraine and stroke is complex and is a continued focus of attention. Several observational studies have identified migraine as an independent risk factor for ischemic stroke. However, a distinction should be made between migraine with and migraine without aura. The migraine-stroke association is mostly apparent for young women with migraine with aura. The association between migraine with aura and stroke is weaker in older age groups, which may be due to the fact that traditional cardiovascular risk factors are more prominent with increasing age. Most studies have not found an association between migraine without aura and ischemic stroke. Although there are several hypotheses about the biologic link between migraine with aura and ischemic stroke, the precise mechanisms remain unclear. However, because the absolute risk of stroke is low in patients with migraine with aura, and migraine without aura is likely not associated with ischemic stroke, most migraine patients will not experience a stroke event.

Opinion statement

Migraine is a pervasive neurologic disorder characterized by recurrent attacks of disabling headache. Despite significant morbidity with impact that may be physical, emotional, social, and economic, treatment of these attacks is often delayed. Patients frequently delay therapy until the more severe or “textbook” symptoms arise, often mistaking the earliest stages as representative of “tension” or “sinus” headaches. Clinicians may recommend deferral of treatment until the more severe levels of pain are seen, perhaps in a misguided attempt to conserve pharmaceutical resources. Patients and clinicians seem more comfortable with perspectives of “being sure it’s a migraine” and “not wasting the medication on milder headaches.” Therefore, patients and clinicians must learn the latest lessons in migraine: 1) mild migraine usually progresses to more severe levels if left untreated, 2) early treatment is more effective than delayed treatment, 3) early treatment may result in lower rates of adverse events and headache recurrence, and 4) early treatment is cost effective. As clinicians advocate the early treatment of migraine in its mild phase, evidence to support this recommendation has finally become available. I educate my migraineurs to consider each typical headache to be a version of migraine. Most patients with migraine will experience “little” headaches that they often mislabel as tension, sinus, regular, stress, or normal headaches. Instead of these terms, I have them consider their attacks as “small migraines” and “big migraines,” with the smaller headaches often evolving into the bigger episodes. Given such a foundation, I advise them to treat at the beginning of the headache, perhaps earlier than they would have previously identified it as a migraine. They must capture the attack while it “whispers migraine” instead of delaying until the attack “shouts migraine.” Early treatment of migraine is successful for most patients. However, there are situations in which treatment of the mild phase is not advisable or possible. In patients with frequent or daily migraine, treatment must be reserved for the most disabling attacks. We must advise treatment as soon as the migraine becomes moderate to severe. Certain patients, or certain headaches in some patients, may not progress through a mild phase, perhaps because of rapid escalation or because migraine is already severe upon awakening. Here we encourage migraineurs to treat as soon as possible, often with parenteral formulations of medication. The reaction of the patient (speed of dosing) and the action of the medication (speed of onset of the drug) will ultimately play roles in the successful interception of each attack.

The pineal gland and its secretory product, melatonin, have been implicated in the pathophysiology of migraine, as well as some of its comorbid disorders. Supporting this view, many migraineurs are susceptible to various environmental triggers that influence the secretion of melatonin from the pineal gland, and many prodromal symptoms are probably generated in the hypothalamus, a brain region that provides input into the pineal gland to modulate the secretion of melatonin. In addition, studies have shown abnormalities in melatonin secretion in patients who experience migraine and an improvement in migraine following administration of melatonin. However, the dysfunction in melatonin secretion in migraineurs may simply be a marker of hypothalamic dysfunction or neuronal hyperexcitability, leading to migraine susceptibility. It is also possible that abnormal melatonin secretion leads to decreased inhibitory neurotransmitter activity, decreased inhibition of the release of calcitonin gene-related peptide (CGRP) from activation of the trigeminal system, or less analgesia.

Whatever its role in the pathogenesis of migraine, melatonin may prove to be a useful therapy. Future studies are necessary to further elucidate whether melatonin is a well tolerated, beneficial therapy, and to determine the optimal dose and formulation of melatonin for use in migraine therapy.

Although the influence of age on the prevalence of migraine is well known, the clinical characterization of migraine across the lifespan remains poorly studied. Limited evidence suggests that migraine attacks get shorter and less typical with advancing age. Similar results were found for transformed migraine at different ages. In this article, we first discuss the prevalence and clinical features of episodic migraine. We then discuss the epidemiology and profile of transformed migraine across the lifespan. Clarifying the influence of age on migraine is of importance for clinical diagnosis and treatment. It also may contain clues to evolving disease biology.

Objective: To determine the efficacy and tolerability of zolmitriptan 2.5mg oral tablet as an acute treatment for menstrual migraine attacks.

Methods: This was a two-phase, multicentre, randomised, double-blind, placebo-controlled, parallel-group outpatient study (phase I is reported here). The study was conducted at 27 sites in the USA. Eligible women were randomised (1 : 1) to receive either zolmitriptan 2.5mg oral tablet or placebo, and instructed to acutely treat up to two menstrual migraine attacks per menstrual period for up to three menstrual cycles with a single dose of study medication. Menstrual migraine was operationally defined as an attack occurring within the time period of 2 days prior to the expected onset of menses to 5 days after the onset of menses. Participants were asked to treat migraine headaches of moderate or severe intensity only that occurred >24 hours after the end of the last migraine attack and that had not been acutely treated with other medications. Information regarding each migraine attack was recorded by patients in treatment diary cards. The primary efficacy variable was 2-hour headache response (defined as a 2-point drop on a 4-point scale) for all attacks treated. Secondary variables included 1-and 4-hour headache response rate; 1-, 2- and 4-hour headache response based on a 100mm visual analogue scale (VAS); pain-free rate at 1, 2 and 4 hours; use of escape medication; the proportion of patients with recurrence within 24 hours of initial treatment; and tolerability.

Conclusion: Oral zolmitriptan is effective and well tolerated for the acute treatment of menstrual migraine attacks. The results are similar to those seen with zolmitriptan in studies of the general migraine population.

Opinion statement

When a patient with migraine has a stroke, all other causes of stroke should be ruled out before the stroke is attributed to migraine. Migraine mimics that present with headaches and stroke, including arteriovenous malformation and cervical carotid artery dissection, should be considered. Patent foramen ovale is a risk factor for both migraine and stroke and should be ruled out with transesophageal echocardiography. A patient with migraine with aura with persistent focal neurologic deficits in the distribution of the typical aura can be diagnosed with migrainous stroke. Patients with migraine with aura with persistent focal neurologic deficits can be treated pharmacologically with intravenous verapamil or magnesium sulfate to relieve the symptoms in familial hemiplegic migraine and sporadic hemiplegic migraine. Prophylactic treatment should be administered to patients with frequent attacks of migraine with aura to prevent recurrence. Oral verapamil is recommended for patients with familial hemiplegic migraine and may be effective in patients with sporadic hemiplegic migraine. Endovascular closure of patent foramen ovale has been reported to prevent recurrence of migraine with aura. The role of patent foramen ovale closure remains controversial pending completion of controlled randomized trials.

Chronic daily headache (CDH) is increasingly recognized as a problem in pediatrics and tertiary pediatric headache care. It is estimated that up to 4% of the adult population has CDH. Many of these are chronic migraine (CM). The fraction of the pediatric population with CDH appears to be lower, although the prevalence has not been adequately determined. The simplest definition of CDH is more than 15 headache days per month. In the International Classification of Headache Disorders, Second Edition (ICHD-II), several types of CDH have been identified. These criteria have been contrasted with the Silberstein-Lipton criteria, with revisions suggested. The diagnosis of CDH is further complicated and may be initiated by the overuse of analgesic medications (medication overuse headache) and requires the resolution of this issue before a final diagnosis can be established. In children, most CDH appears to have migraine features, although it may not completely meet the ICHD-II criteria for migraine or CM. Evaluation of CDH needs to include a complete history and physical examination to identify any possibility of the secondary headaches or headaches directly attributed to a secondary cause. Treatment and management involve a multidisciplinary approach, including acute therapy for when the headache severity increases (while avoiding medication overuse), preventative therapy to reduce the frequency and impact of the CDH, and biobehavioral therapy to assist with long-term outcome.